Neural correlates of probabilistic category learning in patients with schizophrenia.

Functional neuroimaging studies of probabilistic category learning in healthy adults report activation of cortical-striatal circuitry. Based on previous findings of normal learning rate concurrent with an overall performance deficit in patients with schizophrenia, we hypothesized that relative to healthy adults, patients with schizophrenia would display preserved caudate nucleus and abnormal prefrontal cortex activation during probabilistic category learning. Forty patients with schizophrenia receiving antipsychotic medication and 25 healthy participants were assessed on interleaved blocks of probabilistic category learning and control tasks while undergoing blood oxygenation level-dependent functional magnetic resonance imaging.

MicroRNA-338 regulates local cytochrome c oxidase IV mRNA levels and oxidative phosphorylation in the axons of sympathetic neurons.

MicroRNAs (miRs) are evolutionarily conserved, noncoding RNA molecules of approximately 21 nt that regulate the expression of genes that are involved in various biological processes, such as cell proliferation and differentiation. Previously, we reported the presence of a heterogeneous population of mRNAs present in the axons and nerve terminals of primary sympathetic neurons to include the nuclear-encoded mitochondrial mRNA coding for COXIV. Sequence analysis of the 3'UTR of this mRNA revealed the presence of a putative binding site for miR-338, a brain-specific microRNA.

Remission status and cortical thickness in childhood-onset schizophrenia.

Objective: Few studies have examined prediction of schizophrenia outcome in relation to brain magnetic resonance imaging measures. In this study, remission status at the time of discharge was examined in relation to admission cortical thickness for childhood-onset schizophrenia probands. We hypothesized that total, frontal, temporal, and parietal gray matter thickness would be greater in patients who subsequently remit.

Amygdala and orbitofrontal cortex lesions differentially influence choices during object reversal learning.

In nonhuman primates, interaction between the orbitofrontal cortex (OFC) and the amygdala (AMG) has been seen as critical for learning and subsequently changing associations between stimuli and reinforcement. However, it is still unclear what the precise role of the OFC is in altering these stimulus-reward associations, and recent research has questioned whether the AMG makes an essential contribution at all. To gain a better understanding of the role of these two structures in flexibly associating stimuli with reinforcement, we reanalyzed a set of previously published data from groups of monkeys with either OFC or AMG lesions that had been tested on an object reversal learning task.

Increased fear- and stress-related anxiety-like behavior in mice lacking tuberoinfundibular peptide of 39 residues.

Tuberoinfundibular peptide of 39 residues (TIP39) is synthesized by two groups of neurons, one in the subparafascicular area at the caudal end of the thalamus and the other in the medial paralemniscal nucleus within the lateral brainstem. The subparafascicular TIP39 neurons project to a number of brain regions involved in emotional responses, and these regions contain a matching distribution of a receptor for TIP39, the parathyroid hormone 2 receptor (PTH2-R). We have now evaluated the involvement of TIP39 in anxiety-related behaviors using mice with targeted null mutation of the TIP39 gene (Tifp39).

Contextual fear conditioning in humans: cortical-hippocampal and amygdala contributions.

Functional imaging studies of cued fear conditioning in humans have mostly confirmed findings in animals, but it is unclear whether the brain mechanisms that underlie contextual fear conditioning in animals are also preserved in humans. We investigated this issue using functional magnetic resonance imaging and virtual reality contexts. Subjects underwent differential context conditioning in which they were repeatedly exposed to two contexts (CXT+ and CXT-) in semirandom order, with contexts counterbalanced across participants.

Tuberoinfundibular Peptide of 39 residues is required for germ cell development.

Tuberoinfundibular peptide of 39 residues (TIP39) was identified as a PTH 2 receptor ligand. We report that mice with deletion of Tifp39, the gene encoding TIP39, are sterile. Testes contained Leydig and Sertoli cells and spermatogonia but no spermatids.

Progesterone inhibits mature rat dendritic cells in a receptor-mediated fashion.

A variety of extraimmune system factors, including hormones, play a critical role in regulating immunity. Progesterone has been shown to affect immunity in rodents and humans, mainly at concentrations commensurate with pregnancy. These effects are primarily mediated via the progesterone receptor (PR), which acts as a transcription factor, although non-genomic effects of PR activation have been reported.

Identification of tone duration, line length, and letter position: an experimental approach to timing and working memory deficits in schizophrenia.

Patients with schizophrenia display numerous cognitive deficits, including problems in working memory, time estimation, and absolute identification of stimuli. Research in these fields has traditionally been conducted independently. We examined these cognitive processes using tasks that are structurally similar and that yield rich error data.

Scaling and clustering in the study of semantic disruptions in patients with schizophrenia: a re-evaluation.

Some recent studies of semantics in schizophrenia have employed multidimensional scaling and clustering techniques to analyse verbal fluency and triadic comparison data. The conclusions have been: (i) patients generate fewer words in fluency tasks and display more variable similarity groupings of words in triadic tasks, and (ii) this is due to deficits in semantics. We analysed data from both tasks.

Probed recall for serial order deficits in short-term memory in schizophrenic patients.

Background: Patients with schizophrenia frequently display problems in tasks demanding working memory. In a previous study, we examined short-term memory (STM) for serial order by having participants recall lists of letters from the first item to the last item in the order in which they were presented, and we examined the types of errors made (e.g.

The phonological similarity effect in short-term memory serial recall in schizophrenia.

Lists of phonologically similar items are more often recalled in the wrong order than phonologically dissimilar items. At recall, patients with schizophrenia were neither especially susceptible to confusing phonologically similar items nor to making disproportionate movement (i.e.

Semantic clustering in verbal fluency: schizophrenic patients versus control participants.

Background: Schizophrenic patients generate fewer words than healthy controls during verbal fluency tasks. The structure of output may explain why patients generate fewer exemplars.

Methods: Twenty-four healthy controls and 24 patients with schizophrenia participated in six, 3 min semantic fluency tasks.

An investigation of the integrity of semantic boundaries in schizophrenia.

Organizing information and knowledge, and hence categorization, requires specifying boundaries between items, concepts and words. Over-inclusiveness in categorization may be seen as looseness of association; over-inclusive thinking was an early description of schizophrenic thinking. Recent studies suggest semantic memory problems in schizophrenia, and that thought disorder is associated with a disorganized semantic network.

Lithium revisited: savings brought about by the use of lithium, 1970-1991.

Background: Recent estimates of the cost of manic-depressive illness totaled roughly $45 billion in 1991. Using data from the Epidemiological Catchment Area (ECA) study, this study estimates the savings brought about by the use of lithium between 1970 and 1991.

Methods: Total savings are the difference between estimated actual costs and projected costs had lithium never been introduced.

Cognitive impairment in schizophrenia is the core of the disorder.

Patients with schizophrenia exhibit an exceedingly wide range of symptoms from a variety of domains. The cardinal features are abnormal ideas (such as delusions); abnormal perceptions (such as hallucinations); formal thought disorder (as evidenced by disorganized speech); motor, volitional, and behavioral disorders; and emotional disorders (such as affective flattening or inappropriateness). In addition to these diverse, and sometimes bizarre symptoms, it has become increasingly apparent that the disorder is, to variable degrees, accompanied by a broad spectrum of cognitive impairments.

Paired-associate learning and memory interference in schizophrenia.

Patients with frontal lobe damage have been shown to exhibit disproportionate impairments of second list learning as a result of interference effects. Based upon the assumption that schizophrenia is associated with frontal dysfunction, we attempted to explore how various manipulations of paired-associate learning tasks would interfere with schizophrenic patients' memory performance. Patients with schizophrenia were administered four tests of paired-associate learning, in which cue and response words were manipulated to increase interference across two study lists.

Functional magnetic resonance imaging brain mapping in psychiatry: methodological issues illustrated in a study of working memory in schizophrenia.

Functional magnetic resonance imaging (fMRI) is a potential paradigm shift in psychiatric neuroimaging. The technique provides individual, rather than group-averaged, functional neuroimaging data, but subtle methodological confounds represent unique challenges for psychiatric research. As an exemplar of the unique potential and problems of fMRI, we present a study of 10 inpatients with schizophrenia and 10 controls performing a novel "n back" working memory (WM) task.

Norepinephrine metabolism and psychoactive drugs in the endogenous depressions. 1968.

After intraventricular injection of norepinephrine-H3, the concentration of norepinephrine, of normetanephrine and of the deaminated catechols in rat brains was determined, following action of imipramine, desmethylimipramine, chlorpromazine, lithium chloride or cocaine. Following administration of imipramine, desmethylimipramine, and chlorpromazine, norepinephrine concentration decreased significantly at first, had distinctly increased 4.5 hours after imipramine and desmethylimipramine but was normal once again after chlorpromazine.

Availability of tetrahydrobiopterin is not a factor in the inability to detect nitric oxide production by human macrophages.

Human macrophages, in contrast to murine macrophages, do not produce nitric oxide after stimulation with cytokines. This failure has been attributed to the known lack of production by human macrophages of tetrahydrobiopterin, an essential cofactor for nitric oxide synthase. Increasing intracellular levels of tetrahydrobiopterin in cytokine-stimulated murine cells results in an increase in nitrite production.

The corticospinal tract attains a normal configuration in the absence of myelin: observations in jimpy mutant mice.

The corticospinal projection was examined in dysmyelinated, jimpy mice and in unaffected littermates following cortical injections of either wheat germ agglutinin conjugated to horseradish peroxidase or biocytin. Corticospinal axons in both phenotypes traverse the medulla within a well-defined pyramidal tract, decussate within several fascicles at the spinomedullary junction, and extend down the spinal cord in a compact bundle in the ventral-most part of the dorsal funiculus. Very few labeled fibers are seen separated from the main bundle.